The General motors Foundry at Massena, Ny is a designated Superfund Site and has contributed to contamination of soils, sediments, water and air in the vicinity. The contaminants of particular concern to this project are principally polychlorinated biphenyls (PCBs) and to a lesser extent polychlorinated dibenzofurans (PCDFs) and polynuclear aromatic hydrocarbons (PAGs). These substances have accumulated in fish, wildlife and the local human population. This project focuses upon the impact of these substances on a Native American population which lives immediately adjacent to the site, and which is particularly vulnerable to contamination with these chemicals because their traditional life style includes consumption of local fish and wildlife. In our past investigations we have shown that, until recently, there was a clear correlation between fish consumption and levels of PCBs in breast milk, although this relationship has decreased as the population has heeded advisories against fish consumption. The present application is focused on study of physical growth and cognitive development of older children as well as physical and mental health of adults. These studies of the human population are based on previous and concurrent study in animal systems designed to explore the effects of these xenobiotics on neuronal, hormonal and immune systems. The specific hypotheses to be tested are that different congeners have different biologic effects, that congeners of these xenobiotics function as estrogenic or anti-estrogenic agents, interfere with normal thyroid faction, disrupt normal regulation of brain levels of critical neurotransmitters such as dopamine, and interfere with both normal growth and development and cognitive function. We hypothesize that the effects of these substances are different in the developing organism than in adults, and we will explore the biologic effects of both parent compounds and degradation products in in-utero and lactationally exposed rats. Of the ten specific projects, two are focused on study of the Native American population, four are biomedical, two focus on ecology or biodegradation and two are developing technologies that will allow clean up. These research projects will be supported five cores: administration, epidemiology and biostatistics, laboratory services, training and technology transfer and outreach.